tbuckley/cabot-search huggingface dataset:
Cisplatin-induced tinnitus (CIS-TINN) and patient-reported outcomes in adult-onset cancer survivors.
Authors: Megan Shuey, Victoria Sanchez, Paul C. Dinh, Patrick O. Monahan, Howard D. Sesso, Mary Eileen Dolan, Sophie D. Fossa, Lawrence H. Einhorn, David J. Vaughn, Neil E. Martin, Chunkit Fung, Robert D. Frisina, Lois B. Travis
Journal: Journal of Clinical Oncology (2022)

e24089 Background: Cisplatin is one of the most used cytotoxic drugs worldwide, but few studies have comprehensively evaluated CIS-TINN in adult-onset cancer survivors. It is critical to identify survivors with high degrees of handicap and related risk factors, as tinnitus (TINN) is strongly related to adverse health outcomes (AHO) including reduced quality of life, and poorer physical and mental health. Methods: Eligible cisplatin-treated testicular cancer survivors (TCS) (aged &lt; 60 y at diagnosis) completed comprehensive, validated health surveys, including the 20-item Tinnitus Primary Function Questionnaire (TPFQ). TPFQ assesses the 4 main TINN-impaired domains (see Table), each with a response metric of 0% (no interference) to 100% interference by TINN, with final impairment groupings of 0-16% (none/minimal), 17-42% (mild/moderate), and 43-100% (significant). TPFQ measures were compared by 2-sided signed-rank tests. Multinomial logistic regression models (adjusted for age, income, education, yrs since therapy, cisplatin dose, BMI, smoking, hypertension, and hearing loss (HL)) tested for associations with TINN severity. Results are shown as OR [95% CI], p-value. Results: Among 213 TCS [median age 46 y (IQR: 38-52 y); median time since therapy: 10.6 y (IQR: 6.8-16.6 y)], the most common AHOs were CIS-TINN (60%), and HL (60%). For TCS with CIS-TINN, the mean degree of reported interference across all TPFQ domains was 21% (median: 15, IQR: 3-33). TCS with CIS-TINN reported significantly greater interference with emotion (median: 22, range 5-40) than with concentration (median 13, IQR: 1.0-37, p = .004), hearing (median: 10, IQR: 0-30, p &lt; .001), and sleep (median: 2.4, IQR: 0-21, p &lt; .001). Conclusions: Following cisplatin chemotherapy, CIS-TINN is a leading AHO and often reported with HL and reduced quality of life. Severe CIS-TINN was associated with greater handicap on the TPFQ as well as with depression, cognitive dysfunction, and hearing aid use. Overall, however, TCS with CIS-TINN and HL reported underutilization of hearing aids.[Table: see text]
Pyrotinib plus nab-paclitaxel in patients with HER2-positive advanced or metastatic breast cancer: A multicenter, single-arm, open-label phase 2 trial.
Authors: Huan Li, Zhaohui Li, Min Yan, Xiujie Cui, Xuening Ji, Fenqi Fang, Yuyang Zhang, Xiaoxin Wang, Yan Wang, Xiangyu Guo, Mingxi Jing, Zhichao Gao, Hui Cao, Fangyuan Dong, Jie Wu, Cui Jiang, Yangyang Duan, Xiaorui Li, Yujun Jiang, Tao Sun
Journal: Journal of Clinical Oncology (2022)

1035 Background: For human epidermal growth factor receptor 2 (HER2) positive advanced or metastatic breast cancer, the standard therapeutic strategy is HER2-targeted agents combined with a taxane. This multicenter, single-arm phase 2 trial was designed to assess the efficacy and safety of pyrotinib (a brand-new generation, irreversible anti-HER2 tyrosine kinase inhibitor) plus nab-paclitaxel in patients with HER2-positive advanced or metastatic breast cancer. Methods: This was a multicenter, single-arm, open-label phase 2 trial conducted at seven centers in China (ChiCTR1900023653). Women aged 18-75 years, with histologically or cytologically confirmed HER-2 positive (immunohistochemistry [IHC] 3+ or positive confirmed by fluorescence in situ hybridization) advanced or metastatic breast cancer and with Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1 were enrolled. Patients with primary resistance to trastuzumab and bone-only metastases were excluded. Eligible patients received pyrotinib (400 mg, po, qd) plus nab-paclitaxel (125 mg/m 2 , iv, day 1/8/15) for each 28-day cycle until disease progression, unacceptable toxicity, consent withdrawal or death. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included progression-free survival (PFS), overall survival, safety and quality of life. Results: Between December 2019 and December 2021, 51 patients were enrolled. The median age was 55 years (range 35–72). Twenty-three patients (45.1%) had ECOG PS of 0. Ten patients (19.6%) with metastatic disease had previously received first-line treatment and 28 (54.9%) had received prior treatment with trastuzumab. More than half (29 of 51, 56.9%) had hormone receptor-positive disease. Visceral metastases occurred in 56.9% of the patients (29 of 51) and 26 patients (51.0%) were menopausal. The data cutoff for the present analysis was January 21, 2022. Among 38 evaluable patients, four patients (10.5%) had CR, 27 (71.1%) had PR, six (15.8%) had stable disease, and one (2.6%) had progressive disease. The confirmed ORR was 81.6% (95% CI 65.1-91.7%). The PFS data were still immature. The most common grade ≥3 treatment-emergent adverse events included neutropenia (14 of 51, 27.5%), diarrhea (10 of 51, 19.6%), fatigue (5 of 51, 9.8%) and peripheral neuropathy (4 of 51, 7.8%). Conclusions: Pyrotinib combined with nab-paclitaxel showed a promising antitumor activity with good tolerance in patients with HER2-positive advanced or metastatic breast cancer. Clinical trial information: ChiCTR1900023653.
Increasing Black patient participation in metastatic breast cancer clinical trials: The BECOME (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement) project.
Authors: Stephanie Walker, Martha Carlson, Carol B. White, John Howell, Tisha M. Felder
Journal: Journal of Clinical Oncology (2022)

1014 Background: Among U.S. racial/ethnic groups, Black people with breast cancer have the highest death rate and shortest survival. Although ̃15% of cancer patients in the U.S. are Black, only 4-6% of clinical trial participants are Black. Only when trial participants reflect the diversity of the general population can oncologists understand how a drug works across subpopulations. The objectives of the BECOME initiative are to understand barriers to trial participation by Black patients with metastatic breast cancer (MBC) and to identify actions to increase participation. Methods: BECOME is sponsored by the Metastatic Breast Cancer Alliance, a consortium of representatives from nonprofit organizations, pharmaceutical/biotech companies, and patient advocates, many of whom are living with MBC. Findings from a literature review and Key Informant interviews informed a survey of U.S. adults living with MBC. Results: Of 424 survey respondents, 102 (24%) self-identified as Black. Black respondents’ trust and satisfaction with their oncology care team were high (&gt; 90%), and 83% of Black respondents were somewhat or very likely to consider trial participation. However, 40% of Black respondents reported no one on their care team had discussed trials. Black respondents’ reasons to not participate in a trial included concerns about side effects (73%) and effectiveness (63%). Black respondents were more likely than non-Black respondents to believe unstudied treatments may be harmful (57% vs 31%). Black respondents were less likely than non-Black respondents to indicate they trust trials (73% vs 91%) and trust that people of all races/ethnicities get fair treatment in trials (32% vs 56%). Black respondents were more likely than non-Black respondents to value receiving trial information from someone with the same racial/ethnic identity (67% vs 10%), who has had breast cancer (73% vs 44%) or MBC (73% vs 51%), or who has been in a trial (72% vs 48%). Black respondents were also more likely to be motivated to participate to ensure people with their racial or ethnic identity will benefit (83% vs 51%). Conclusions: Black patients with MBC are willing to consider participating in clinical trials. Actionable steps to increase Black patient participation include: 1) enhancing awareness about trials by informing patients, increasing education, training healthcare providers to deliver patient-friendly information in an unbiased manner, and providing messaging from people of shared racial/ethnic identity and health experience; 2) building trust through clear communication; 3) addressing concerns about side effects, effectiveness, harm, and fair treatment; and 4) helping patients find and access trials. All stakeholder groups have a role to play in increasing Black patient participation in MBC clinical trials.
Real-world effectiveness of anlotinib plus PD-1 inhibitors as chemo-free therapy in advanced or metastatic esophageal cancer.
Authors: Junsheng Wang, Yonggui Hong, Tao Wu, Ping Lu, Zhiwei Chang, Wei Liang, Guifang Zhang
Journal: Journal of Clinical Oncology (2022)

e16052 Background: Immunotherapy, particularly with anti-PD-1/PD-L1 antibodies, has shown therapeutic efficacy in various malignancies. Compared with chemotherapy, anti-PD-1 antibody monotherapy improved the median overall survival in advanced or metastatic esophageal cancer. The combination of an anti-PD-1/PD-L1 antibody with an angiogenesis inhibitor has shown efficacy in many cancers which including esophageal cancer. The purpose of this study is to investigate the efficacy and safety of anlotinib plus PD-1 inhibitors as chemo-free therapy during the treatment of esophageal cancer in the real world setting. Methods: This prospective, multicenter real-world study (NCT04966611) evaluated the efficacy and safety of anlotinib plus PD-1 inhibitors in the chemo-free therapy setting for advanced or metastatic esophageal cancer patients (pts). Primary endpoint was evaluation of PFS (progression-free survival), and secondary endpoints included ORR (objective response rate), DCR (disease control rate) and OS (overall survival). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: Between May 2020 and Dec 2021, 50 pts were enrolled. 45 comprised the evaluable population. In the full analysis set, 44 had squamous cell and 1 patient had adenocarcinoma histology. 29 (64.4%) of 45 pts were male. 10 (22.2%) had an ECOG performance status of 0, 32 (71.1%) status of 1 and 3 (6.7%) status of 2. Twenty (44.4%) pts had distant metastases and 29(64.4%) pts had comorbidities. 15 pts had previously used anti-PD-1/PD-L1 antibody or vascular targeting drugs, of which 5 cases had combined the two drugs. Among all evaluable pts, 5(11.1%) pts received first-line, 27(60.0%) second-line and 13(28.9%) third &amp; above line therapy. Among all pts, 1 patient achieved complete response (CR), 16 pts partial response (PR), 25 pts stable disease (SD), illustrating an ORR of 37.8% and a DCR of 93.3%. In the first line therapy, ORR was 60.0%, DCR was 100%.In the second line therapy, ORR was 37.0%, DCR was 96.3%. In the third &amp; above line, ORR with 30.8%, DCR with 84.6% was observed. Median PFS was not reached. Treatment related adverse events (trAEs) were reported in 24 pts(53.3%). No patient had grade 3 or more trAEs. Conclusions: Anlotinib plus PD-1 inhibitors in chemo-free therapy for advanced or metastatic esophageal cancer was active and showed excellent tumor response and was generally well tolerated. Further investigation is required in a larger real-world cohort to validate the benefit of anlotinib plus PD-1 inhibitor in esophageal cancer. Clinical trial information: NCT04966611.
Cytoprotection of Human Progenitor and Stem Cells through Encapsulation in Alginate Templated, Dual Crosslinked Silk and Silk–Gelatin Composite Hydrogel Microbeads
Authors: Onur Hasturk, Jordan A. Smiley, Miles Arnett, Jugal Kishore Sahoo, Cristian Staii, David L. Kaplan
Journal: Advanced Healthcare Materials (2022)

Susceptibility of mammalian cells against harsh processing conditions limit their use in cell transplantation and tissue engineering applications. Besides modulation of the cell microenvironment, encapsulation of mammalian cells within hydrogel microbeads attract attention for cytoprotection through physical isolation of the encapsulated cells. The hydrogel formulations used for cell microencapsulation are largely dominated by ionically crosslinked alginate (Alg), which suffer from low structural stability under physiological culture conditions and poor cell-matrix interactions. Here the fabrication of Alg templated silk and silk/gelatin composite hydrogel microspheres with permanent or on-demand cleavable enzymatic crosslinks using simple and cost-effective centrifugation-based droplet processing are demonstrated. The composite microbeads display structural stability under ion exchange conditions with improved mechanical properties compared to ionically crosslinked Alg microspheres. Human mesenchymal stem and neural progenitor cells are successfully encapsulated in the composite beads and protected against environmental factors, including exposure to polycations, extracellular acidosis, apoptotic cytokines, ultraviolet (UV) irradiation, anoikis, immune recognition, and particularly mechanical stress. The microbeads preserve viability, growth, and differentiation of encapsulated stem and progenitor cells after extrusion in viscous polyethylene oxide solution through a 27-gauge fine needle, suggesting potential applications in injection-based delivery and three-dimensional bioprinting of mammalian cells with higher success rates.
Preliminary safety and efficacy of camrelizumab plus nab-paclitaxel and carboplatin as frontline setting in extensive-stage small cell lung cancer (ES-SCLC) from a phase II trial.
Authors: Shengxiang Ren, Jia Yu, Anwen Xiong, Qi Wang, Lei Wang, Bin Chen, Menghang Yang, Wei Li, Jiajia Yuan, Changhong Zhao, Caicun Zhou
Journal: Journal of Clinical Oncology (2022)

8564 Background: Impower133 and CASPIAN studies showed that PD-L1 antibody combined with first-line chemotherapy could prolong the overall survival. Our previous study showed that nab-paclitaxel had a promising efficacy as later line setting in ES-SCLC. This phase II trial aimed to evaluate the efficacy and safety of camrelizumab plus nab-paclitaxel and carboplatin as front-line setting in ES-SCLC. Methods: Key inclusion factors were18-75 years old, histologically or cytologically confirmed ES-SCLC, ECOG performance status 0-1, no previous systematic treatment. Patients (pts) received 4 ̃ 6 cycles of camrelizumab (200mg, D1, q3w) combined with nab-paclitaxel (230mg/kg, D1, q3w) plus carboplatin (AUC = 5, D1, q3w), then camrelizumab maintenance until disease progression or intolerable side effects. The primary endpoint was 6 months progression free survival rate. Secondary endpoints included PFS, ORR and safety. Results: From April 2021 to December 2021, 36 pts who received at least one dose of camrelizumab were included into this report. The median age was 60.5 (range: 32-73) with 30 (83.3%) males, 19 (52.8%) former smokers, and 36 (100%) ECOG performance status 1. The median drug exposure was 5 cycles, and 18 (50%) pts entered the maintenance stage. 33 pts had at least one 1 post-treatment tumor assessment. Among them, 32 partial responses (5 unconfirmed), 1 progressive disease (new lesion). The confirmed ORR was 81.8% (27/33), the unconfirmed ORR was 97% (32/33), DCR was 97% (32/33). The median PFS was 7.27 months (95% CI: 4.7 – 9.8 months). 24 (66.7%) pts had at least one adverse event, and 10 (27.8%) pts experienced grade 3 or 4 adverse events, including 10 (27.8%) neutropenia, 4 (11.1%) leukopenia, 2 (5.6%) thrombocytopenia, 2 (5.6%) anemia, 2 (5.6%) hepatic function abnormal,1(2.8%) alanine aminotransferase increased, 1(2.8%) hyperglycaemia, 1(2.8%) diabetes mellitus, and no grade 5 adverse event happened. Conclusions: Camrelizumab plus nab-paclitaxel and carboplatin had promising efficacy and safety profile as first-line setting in ES-SCLC, further validation is warranted. Clinical trial information: NCT04790539.
Effect of lung cancer screening on the incidence of advanced lung cancer in the United States: A SEER database analysis.
Authors: Maxwell Oluwole Akanbi, Orimisan Samuel Adekolujo, Dan Isaac, Ahsan Wahab, Ling Wang, Borys Hrinczenko
Journal: Journal of Clinical Oncology (2022)

10506 Background: In 2013, the USPSTF recommended screening for lung cancer with low-dose chest computed tomography (LDCT). This was based on the results of the National Lung Screening Trial which showed a 20% relative reduction in mortality from LDCT compared with chest radiography. In Feb/March 2015, the Centers for Medicare and Medicaid (CMS) provided screening guidelines and they and private insurers started covering the cost of LDCT. The impact of this recommendation in the real-world setting is unknown. We investigated the impact of LDCT recommendations on the incidence of advanced lung cancer (a-LCa) in the US general population. We sought to verify that the implementation of LDCT will yield an earlier lung cancer diagnosis and thereby reduce the incidence of later stages of lung cancer. Methods: From the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, we identified adults 55-80 years diagnosed with regional or metastatic (advanced) lung cancer from 2004 to 2018. Age-adjusted incidence rates (AAIR) of advanced lung cancer in 2004-2014 (Pre-LDCT) and 2015-2018 (Post-LDCT) were compared using interrupted time series (ITS) regression analyses. Analyses were stratified by sex, race, and residence. Results: A total of 400,343 patients who met the study criteria were included. Of these, 219,828 (55%) were women and 76% (n = 304,801) were non-Hispanic White. At all periods, the AAIR of a-LCa was highest in non-Hispanic Blacks. Overall, there was a 41% decline in the AAIR of a-LCa in the post-LDCT period compared to the pre-LDCT era (Annual decline of 7.6 vs 4.5 /100,000 person-years (PY) for 2015-2018 vs 2004-2014, p &lt; 0.01). Women experienced a more accelerated decline in the AAIR of a-LCa compared to men (53% versus 30%). By race, the annual rates of a-LCa declined most rapidly among non-Hispanic Blacks (55%, 9.5/ 100,000 PY, 2015-2018 vs 4.7/100,000 PY, 2004-2014, p &lt; 0.01), and the slowest rate of decline was among Hispanics (41%, 4.6/100,000 PY,2015-2018 vs 2.7/100,000 PY, 2004-2014, p &lt; 0.01). By residence, non-metropolitan dwellers experienced a greater decline in annual rates of a-LCa compared with metropolitan dwellers (non-Metropolitan: 69%, 10.1/100,000 PY, 2015-2018 vs 3.2/100,000 PY 2003-2014, p &lt; 0.01: Metropolitan dwellers: 37%, 7.2/100,000 PY 2015-2018 vs 4.5/100,000 PY, p &lt; 0.01). Conclusions: Using population-based data we found a significant decline in rates of a-LCa following the adoption of LDCT for lung cancer screening in the US. Rates of decline in the incidence of a-LCa, however, varied among subgroups. Non-Hispanic Blacks, women, and rural dwellers experienced the most decline in annual rates of a-LCa from 2015 to 2018. Our study shows the overall benefit of LDCT in marginalized communities. However, the impact of our findings on lung cancer mortality will still need further study.
Images Are Data: Challenges and Opportunities in the Clinical Translation of Radiomics
Authors: Wei Mu, Matthew B. Schabath, Robert J. Gillies
Journal: Cancer Research (2022)

Abstract Radiomics provides an opportunity to uncover image-based biomarkers through the conversion and analysis of standard-of-care medical images into high-dimensional mineable data. In the last decade, thousands of studies have been published on different clinical applications, novel analysis algorithms, and the stability and reproducibility of radiomics. Despite this, interstudy comparisons are challenging because there is not a generally accepted analytic and reporting standard. The ability to compare and combine results from multiple studies using interoperative platforms is an essential component on the path toward clinical application. The NCI supported study from van Griethuysen and colleagues published in Cancer Research in 2017 proposed PyRadiomics: an open-source radiomics quantification platform for standardized image processing. Since released, it has become a frequently utilized analytic tool in the radiomics literature and has accelerated the capability of combining data from different studies. The subsequent challenge will be the design of multicenter trials with a fixed and immutable version of software, which is currently open-source, readily modified and freely distributed. Generally, this is accomplished with a commercial partner to navigate the regulatory processes. See related article by van Griethuysen and colleagues, Cancer Res 2017;77:e104–7.
EPCT-06. Phase I study of ribociclib and everolimus post-radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG): Updated report from the COllaborative Network for NEuro-Oncology Clinical Trials (CONNECT)
Authors: Margot A Lazow, Mariko DeWire, Olivia Campagne, James L Leach, Christine Fuller, Shiva Senthil Kumar, Joseph Stanek, Peter de Blank, Trent R Hummel, Natasha Pillay-Smiley, Ralph Salloum, Charles B Stevenson, Patricia Baxter, David Gass, Stewart Goldman, Sarah E S Leary, Adam Carle, Adam Lane, Rachid Drissi, Clinton Stewart, Maryam Fouladi
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Dual inhibition of CDK4/6 and mTOR in DIPG and pediatric HGG has strong biologic rationale, given prevalent genetic alterations resulting in upregulated cell cycle and PI3K/mTOR pathways in these diseases, as well as non-overlapping agent toxicities. This study sought to evaluate safety/tolerability and determine the recommended phase 2 dose (RP2D) of ribociclib and everolimus among children with newly diagnosed DIPG and HGG post-radiotherapy. METHODS: Patients were enrolled according to a Rolling-6 design and received oral ribociclib and everolimus once daily for 21 and 28 days, respectively, starting 2-4 weeks post-completion of radiotherapy. All HGG and biopsied DIPG patients were screened for RB protein presence by immunohistochemistry. Pharmacokinetics and survival data were analyzed. RESULTS: Nineteen patients enrolled (median age: 8 years [range: 2-18]). Three patients enrolled at each of dose levels 1 and 2 without dose-limiting toxicities (DLTs). Thirteen patients enrolled at dose level 3, with one patient experiencing a DLT (grade 3 infection). One patient came off therapy prior to cycle 9 due to cardiac toxicity. The most common grade 3/4 toxicities were neutropenia (33%), leucopenia (17%), and lymphopenia (11%). Steady-state everolimus exposures in combination were 1.9±0.9-fold higher than single-agent administration. Median overall survival (OS) for 15 patients with DIPG was 13.9 months, with 12-, 24-, and 36-month OS of 53.3%, 38.9%, and 38.9%. Median event-free survival for four patients with HGG was 10.5 months. Among patients with tumor molecular profiling, two longer survivors (OS: 20, &amp;gt;37 months) had evidence of cell cycle upregulation with CDKN2A/B deletion and CDK4 overexpression identified. CONCLUSIONS: The combination of ribociclib and everolimus was well-tolerated post-radiotherapy in children with newly diagnosed DIPG and HGG, with a RP2D of ribociclib 170 mg/m2 days 1-21 and everolimus 1.5 mg/m2 days 1-28. Results will inform a molecularly-guided phase II study currently underway to evaluate efficacy.